Ca²⁺, heat, and mitochondrial biogenesis.

<p>The contraction of skeletal muscle fibers is initiated by sarcoplasmic reticulum (SR) Ca²⁺ release via the ryanodine receptors (RyR), which is triggered by action potential activation of the transverse tubular voltage sensors, the dihydropyridine receptors (DHPR). Ca²⁺ activates the contractile machinery and is subsequently pumped back into the SR via SERCA (dashed arrows). α-Actinin 3 deficiency results in increased protein expression of SERCA and the SR Ca²⁺ buffers calsequestrin (CSQ) (grey arrows) and sarcalumenin (not shown). These changes are accompanied by increased SR Ca²⁺ leak and, subsequently, increased Ca²⁺ reuptake (red arrows), which generates heat. Increased [Ca²⁺] in the cytosol can trigger calcineurin (CaN) and calmodulin kinase (CaMK), resulting in PGC-1α activation (blue arrows) and subsequent mitochondrial biogenesis (green arrow).</p

Additional file 1: Figure S1. of Impaired Ca2+ release contributes to muscle weakness in a rat model of critical illness myopathy

Coomassie protein staining. Membranes used for western blot analysis of Na+ channels, DHPR (left panel), RyR1and SERCA1 (right panel). Lanes are marked as SHAM (S) or ICU (I); the value 110 kDa refers to the protein marker size in the ladder lane (PDF 5931 kb

Additional file 2: Figure S2. of Impaired Ca2+ release contributes to muscle weakness in a rat model of critical illness myopathy

Typical examples of the negative controls obtained for Na+ channels, DHPR, RyR and SERCA1 immunohistochemical staining (PDF 871 kb